glycogen and Cardiovascular-Diseases

The prevalence of cardiometabolic disease has reached an exponential rate of rise over the last decades owing to high fat/high caloric diet intake and satiety life style. Although the presence of dyslipidemia, insulin resistance, hypertension and obesity mainly contributes to the increased incidence of cardiometabolic diseases, population-based, clinical and genetic studies have revealed a rather important role for inherited myopathies and endocrine disorders in the ever-rising metabolic anomalies. Inherited metabolic and endocrine diseases such as glycogen storage and lysosomal disorders have greatly contributed to the overall prevalence of cardiometabolic diseases. Recent evidence has demonstrated an essential role for proteotoxicity due to autophagy failure and/or dysregulation in the onset of inherited metabolic and endocrine disorders. Given the key role for autophagy in the degradation and removal of long-lived or injured proteins and organelles for the maintenance of cellular and organismal homeostasis, this mini-review will discuss the potential contribution of autophagy dysregulation in the pathogenesis of inherited myopathies and endocrine disorders, which greatly contribute to an overall rise in prevalence of cardiometabolic disorders. Molecular, clinical, and epidemiological aspects will be covered as well as the potential link between autophagy and metabolic anomalies thus target therapy may be engaged for these comorbidities.

Topics: Autophagy; Cardiovascular Diseases; Endocrine System Diseases; Glycogen; Homeostasis; Humans; Insulin Resistance; Lysosomes; Metabolic Syndrome; Metabolism, Inborn Errors; Muscular Diseases; Obesity

Recently, diets low in carbohydrate content have become a matter of international attention because of the WHO recommendations to reduce the overall consumption of sugars and rapidly digestible starches. One of the common metabolic changes assumed to take place when a person follows a low-carbohydrate diet is ketosis. Low-carbohydrate intakes result in a reduction of the circulating insulin level, which promotes high level of circulating fatty acids, used for oxidation and production of ketone bodies. It is assumed that when carbohydrate availability is reduced in short term to a significant amount, the body will be stimulated to maximize fat oxidation for energy needs. The currently available scientific literature shows that low-carbohydrate diets acutely induce a number of favourable effects, such as a rapid weight loss, decrease of fasting glucose and insulin levels, reduction of circulating triglyceride levels and improvement of blood pressure. On the other hand some less desirable immediate effects such as enhanced lean body mass loss, increased urinary calcium loss, increased plasma homocysteine levels, increased low-density lipoprotein-cholesterol have been reported. The long-term effect of the combination of these changes is at present not known. The role of prolonged elevated fat consumption along with low-carbohydrate diets should be addressed. However, these undesirable effects may be counteracted with consumption of a low-carbohydrate, high-protein, low-fat diet, because this type of diet has been shown to induce favourable effects on feelings of satiety and hunger, help preserve lean body mass, effectively reduce fat mass and beneficially impact on insulin sensitivity and on blood lipid status while supplying sufficient calcium for bone mass maintenance. The latter findings support the need to do more research on this type of hypocaloric low-carbohydrate diet.

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Diet, Carbohydrate-Restricted; Diet, Reducing; Dietary Carbohydrates; Energy Metabolism; Glycogen; Humans; Insulin; Insulin Resistance; Insulin Secretion; Lipids; Neoplasms; Osteoporosis, Postmenopausal; Risk Factors

Topics: Amino Acids; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Energy Metabolism; Fasting; Gluconeogenesis; Glucose Intolerance; Glycated Hemoglobin; Glycogen; Humans; Lipid Metabolism; Liver; Risk

Insulin resistance is defined as a clinical state in which a normal or elevated insulin level produces an attenuated biologic response. Specifically, the biologic response most studied is insulin-stimulated glucose disposal, yet the precise cellular mechanism responsible is not yet known. However, the presence of insulin resistance is observed many years before the onset of clinical hyperglycemia and the diagnosis of Type 2 diabetes. Insulin resistance at this stage appears to be significantly associated with a clustering of cardiovascular risk factors predisposing the individual to accelerated cardiovascular disease. An overview of insulin resistance and the associated clinical insulin resistant state will be discussed.

Topics: Animals; Biological Transport; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose; Glycogen; Humans; Hyperglycemia; Insulin; Insulin Resistance; Models, Chemical; Signal Transduction; Syndrome

The rationale for the concurrent prescription of beta-blockers and programmes of exercise is that both medication and physical activity can improve the quality of life of patients with cardiovascular disease. Difficulties arise when drugs reduce either the physical ability or the motivation to exercise. This article focuses on the physiological limitations to prolonged aerobic exercise in patients receiving beta-blockers. Possible limiting factors to exercise while taking beta-blockers include reduction in heart rate and cardiac output, local alterations to blood flow, changes to muscle and liver glycogenolysis, and alterations to adipose and intra-muscular lipolysis. The disadvantages and advantages of nonselective and beta 1-selective drugs are discussed, as well as those of drugs that have beta 2-agonist properties. Particular emphasis is placed upon the beta-blocker-induced attenuation of the normal increase in fat oxidation during prolonged exercise. There are physiological advantages, especially for the physically active individual, in prescribing beta 1-selective rather than nonselective drugs in controlled release, rather than conventional release, form. Additionally, there may be further advantages in prescribing drugs which have partial agonist properties at beta 2 receptors.

Topics: Adipose Tissue; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Cardiac Output; Cardiovascular Diseases; Delayed-Action Preparations; Exercise; Glycogen; Heart Rate; Humans; Lipid Metabolism; Liver; Metabolism; Muscle, Skeletal; Quality of Life

Treatment with tyrosine kinase inhibitors (TKIs), especially nilotinib, often results in hyperglycemia, which may further increase cardiovascular disease risk in patients with chronic myeloid leukemia (CML). The mechanism underlying the TKI-induced glucose dysregulation is not clear. TKIs are suggested to affect insulin secretion but also insulin sensitivity of peripheral tissue has been proposed to play a role in the pathogenesis of TKI-induced hyperglycemia. Here, we aimed to assess whether skeletal muscle glucose uptake and insulin responses are altered in nondiabetic patients with CML receiving TKI treatment. After a glycogen-depleted exercise bout, an intravenous glucose bolus (0.3 g/kg body weight) was administered to monitor 2-h glucose tolerance and insulin response in 14 patients with CML receiving nilotinib, 14 patients with CML receiving imatinib, and 14 non-CML age- and gender-matched controls. A dynamic [

Topics: Blood Glucose; Cardiovascular Diseases; Fluorodeoxyglucose F18; Glucose; Glycogen; Humans; Hyperglycemia; Imatinib Mesylate; Insulin; Insulin Resistance; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Pyrimidines; Tyrosine Kinase Inhibitors

Cardiovascular diseases are among the primary life-threatening conditions affecting human society. Intermittent fasting is shown to be functional in the prevention of cardiovascular diseases, however, the information on fasting-associated modifications in myocardial biomolecules is limited. This study aimed to determine the impact of 18-h intermittent fasting administered for five weeks on 12 months-old rats using supervised linear discriminant analysis and support vector machine algorithms constructed on spectrochemical data obtained from myocardial tissues. These algorithms revealed gross biomolecular modifications, while quantitative analyses demonstrated higher amounts of saturated lipids (19%), triglycerides (11%), and lipids (56%), in addition to enhancement in membrane dynamics (18%). The concentrations of nucleic acids and glucose are increased by 52%, while the glycogen content is diminished by 61%. The protein carbonylation/oxidation is reduced by 38%, whereas a 35% increase in protein content was measured. Phosphorylated proteins have been calculated to be at higher concentrations in the 13-62% range. The study findings demonstrated significant molecular changes in the myocardium of rats subjected to intermittent fasting.

Topics: Animals; Cardiovascular Diseases; Fasting; Glycogen; Humans; Infant, Newborn; Lipids; Myocardium; Rats

AMPK activated protein kinase (AMPK), a master regulator of energy homeostasis, is activated in response to an energy shortage imposed by physical activity and caloric restriction. We here report on the identification of PAN-AMPK activator O304, which - in diet-induced obese mice - increased glucose uptake in skeletal muscle, reduced β cell stress, and promoted β cell rest. Accordingly, O304 reduced fasting plasma glucose levels and homeostasis model assessment of insulin resistance (HOMA-IR) in a proof-of-concept phase IIa clinical trial in type 2 diabetes (T2D) patients on Metformin. T2D is associated with devastating micro- and macrovascular complications, and O304 improved peripheral microvascular perfusion and reduced blood pressure both in animals and T2D patients. Moreover, like exercise, O304 activated AMPK in the heart, increased cardiac glucose uptake, reduced cardiac glycogen levels, and improved left ventricular stroke volume in mice, but it did not increase heart weight in mice or rats. Thus, O304 exhibits a great potential as a novel drug to treat T2D and associated cardiovascular complications.

Topics: AMP-Activated Protein Kinases; Animals; Blood Glucose; Blood Pressure; Cardiomegaly; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose; Glycogen; Heart; Heterocyclic Compounds; Holoprosencephaly; Homeostasis; Humans; Insulin Resistance; Insulin-Secreting Cells; Jaw Abnormalities; Metformin; Mice; Mice, Obese; Muscle, Skeletal; Rats; Stroke Volume

What is the central question of this study? Can long-term leucine supplementation prevent prolonged strenuous endurance exercise induced cardiac injury? What is the main finding and its importance? Prolonged endurance exercise does not seem to exceed cardiac energetic capacity, hence it does not represent an energy threat to this organ, at least in trained subjects. However, it may induce, in susceptible individuals, a state of cardiac electrical instability, which has been associated with ventricular arrhythmias and sudden cardiac death. This situation might be worsened when combined with leucine supplementation, which leads to increased blood pressure and cardiac injury. Leucine supplementation failed to prevent cardiac fatigue symptoms and may aggravate prolonged strenuous exercise-induced cardiovascular disturbances in trained rats. Observational studies have raised concerns that prolonged strenuous exercise training may be associated with increased risk of cardiac arrhythmia and even primary cardiac arrest or sudden death. It has been demonstrated that leucine can reduce prolonged exercise-induced muscle damage and accelerate the recovery process. The aim of this study was to investigate the effects of prolonged strenuous endurance exercise on cardiovascular parameters and biomarkers of cardiac injury in trained adult male rats and assess the use of leucine as an auxiliary substance to prevent the likely cardiac adverse effects caused by strenuous exercise. Twenty-four male Wistar rats were randomly allocated to receive a balanced control diet (18% protein) or a leucine-rich diet (15% protein plus 3% leucine) for 6 weeks. The rats were submitted to 1 h of exercise, 5 days per week for 6 weeks. Three days after the training period, the rats were submitted to swimming exercise until exhaustion, and cardiac parameters were assessed. Exercising until exhaustion significantly increased cardiac biomarker levels, cytokines and glycogen content inhibited protein synthesis signalling and led to cardiac electrical disturbances. When combined with exercise, leucine supplementation led to greater increases in the aforementioned parameters and also a significant increase in blood pressure and protein degradation signalling. We report, for the first time, that leucine supplementation not only fails to prevent cardiac fatigue symptoms, but may also aggravate prolonged strenuous exercise-induced cardiovascular disturbances in trained rats. Furthermore, we find that

Topics: Animals; Biomarkers; Cardiovascular Diseases; Cardiovascular System; Cytokines; Diet; Dietary Supplements; Fatigue; Glycogen; Leucine; Male; Muscle, Skeletal; Physical Conditioning, Animal; Physical Endurance; Rats; Rats, Wistar; Swimming

Efficacy of Kalpaamruthaa on the activities of lipid and carbohydrate metabolic enzymes, electron transport chain complexes and mitochondrial ATPases were studied in heart and liver of experimental rats. Cardiovascular damage (CVD) was developed in 8 weeks after type 2 diabetes mellitus induction with high fat diet (2 weeks) and low dose of streptozotocin (2 × 35 mg/kg b.w. i.p. in 24 hr interval). In CVD-induced rats, the activities of total lipase, cholesterol ester hydrolase and cholesterol ester synthetase were increased, while lipoprotein lipase and lecithin-cholesterol acyltransferase activities were decreased. The activities of lipid-metabolizing enzymes were altered by Kalpaamruthaa in CVD-induced rats towards normal. Kalpaamruthaa modulated the activities of glycolytic enzymes (hexokinase, phosphogluco-isomerase, aldolase and glucose-6-phosphate dehydrogenase), gluconeogenic enzymes (glucose-6-phosphatase and fructose-1, 6-bisphosphatase) and glycogenolytic enzyme (glycogen phosphorylase) along with increased glycogen content in the liver of CVD-induced rats. The activities of isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, α-ketoglutarate dehydrogenase, Complexes and ATPases (Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase) were decreased in CVD-induced rats, which were ameliorated by the treatment with Kalpaamruthaa. This study ascertained the efficacy of Kalpaamruthaa for the treatment of CVD in diabetes through the modulation of metabolizing enzymes and mitochondrial dysfunction.

Topics: Adenosine Triphosphatases; Animals; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Glycogen; Heart; Lipid Metabolism; Liver; Magnoliopsida; Male; Medicine, Ayurvedic; Mitochondria; Phytotherapy; Plant Extracts; Rats, Sprague-Dawley

Pompe disease is a lysosomal storage disease caused by the absence of acid alpha-1,4 glucosidase (GAA). The pathophysiology of Pompe disease includes generalized myopathy of both cardiac and skeletal muscle. We sought to use recombinant adeno-associated virus (rAAV) vectors to deliver functional GAA genes in vitro and in vivo. Myotubes and fibroblasts from Pompe patients were transduced in vitro with rAAV2-GAA. At 14 days postinfection, GAA activities were at least fourfold higher than in their respective untransduced controls, with a 10-fold increase observed in GAA-deficient myotubes. BALB/c and Gaa(-/-) mice were also treated with rAAV vectors. Persistent expression of vector-derived human GAA was observed in BALB/c mice up to 6 months after treatment. In Gaa(-/-) mice, intramuscular and intramyocardial delivery of rAAV2-Gaa (carrying the mouse Gaa cDNA) resulted in near-normal enzyme activities. Skeletal muscle contractility was partially restored in the soleus muscles of treated Gaa(-/-) mice, indicating the potential for vector-mediated restoration of both enzymatic activity and muscle function. Furthermore, intramuscular treatment with a recombinant AAV serotype 1 vector (rAAV1-Gaa) led to nearly eight times normal enzymatic activity in Gaa(-/-) mice, with concomitant glycogen clearance as assessed in vitro and by proton magnetic resonance spectroscopy.

Topics: alpha-Glucosidases; Animals; Cardiovascular Diseases; Dependovirus; Disease Models, Animal; Fibroblasts; Gene Expression Regulation; Genetic Therapy; Genetic Vectors; Glycogen; Glycogen Storage Disease Type II; Homozygote; Humans; Immunoenzyme Techniques; Infant; Lysosomal Storage Diseases; Mice; Mice, Inbred BALB C; Mice, Knockout; Muscle, Skeletal; Myocardium; Transduction, Genetic

Topics: Animals; Apoptosis; Cardiovascular Diseases; Cardiovascular System; Cytoprotection; Disease Susceptibility; Enzyme Activation; Estrogens; Female; Glycogen; Humans; Insulin-Like Growth Factor I; Isoenzymes; Male; Mice; Mice, Transgenic; Myocardium; Phosphatidylinositol Phosphates; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Sex Factors; Signal Transduction; Transcription Factors

Topics: Adult; Aged; Aging; Cardiovascular Diseases; Energy Metabolism; Glycogen; Humans; Life Style; Lipid Metabolism; Muscle, Skeletal; Oxygen Consumption; Risk Factors

The metabolic changes in the heart--increased glycogen, triglycerides, and cyclic AMP, and decreased ATP and creatine phosphate--indicate that diabetes is a generalized disorder of cellular metabolism. The summarized observations provide additional biochemical reasons for early detection and treatment of patients with diabetes mellitus. Cognizance of three metabolic events are relevant to the treatment of the diabetic patient during acute cardiac events such as myocardial infarction.

Topics: Adenosine Triphosphate; Cardiovascular Diseases; Cyclic AMP; Diabetes Complications; Diabetes Mellitus; Glycogen; Humans; Myocardium; Phosphocreatine; Triglycerides

As a contribution to the aetiology of insufficiency of placenta carbohydrate-histo-chemical investigations of the kyema were per-formed from the 10 th to 14 th week of pregnancy. The studies were carried out on pregnancy products of women with affection of kidneys, circulatory failures, and under cytostatic therapy. For comparison purposes, cases were used where the pregnancy was without organic diseases of the pregnant women. The investigations performed did not prove evidence of an essential alteration of the regulation of carbohydrates in the kyema by maternal disorders or cytostatic treatment during early gravidity.

Topics: Adrenal Glands; Adult; Antineoplastic Agents; Carbohydrates; Cardiovascular Diseases; Decidua; Embryo, Mammalian; Extraembryonic Membranes; Female; Glycogen; Histocytochemistry; Humans; Kidney; Kidney Diseases; Liver; Placenta Diseases; Placental Insufficiency; Pregnancy; Pregnancy Trimester, First; Trophoblasts

Topics: Animals; Cardiovascular Diseases; Cell Membrane; Connective Tissue; Coronary Vessels; Glycogen; Heart; Histocytochemistry; Methods; Mitochondria, Muscle; Myocardium; Myofibrils; Rabbits; Radiation Effects

Topics: Adult; Anemia, Hemolytic; Cardiovascular Diseases; Chronic Disease; Diabetes Mellitus; Female; Gastrointestinal Diseases; Gestational Age; Glycogen; Humans; Hyperthyroidism; Infant, Newborn; Liver Diseases; Neoplasms; Nephritis, Interstitial; Postpartum Period; Pregnancy; Respiratory Tract Diseases

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Cardiovascular Diseases; Glycogen; Myocardium; Phosphocreatine; Rabbits